In histology, there are four kinds of tissue: epithelial, connective, muscle, and nervous.  Epithelial tissue is the most varied in shape as it has to accomplish many, many types of function.  Thus, this section will review the ways to classify epithelial tissue.

Epithelial tissue form the covering of all body surfaces – both external and interna. Epithelial tissue line external body (e.g. skin), internal cavities (e.g. inside blood vessels), and hollow organs (e.g. the stomach). They are also the major tissue in glands which secrete substances (e.g. oil gland on hair follicles, pancreatic duct that deliver enzymes from pancreas into GI tract). They perform a variety of functions and that is why they have different layers of cells (dependent on the function) and specialized shapes to help it achieve its function.

An analogy for why there are different layers & shapes is to consider the different kind of skins/rinds on fruit. The skin/rind on a grape is a different thickness to a watermelon, probably due to the fact that grapes usually are suspended in the air whereas watermelon grows on the ground and the fact that the watermelon weights more than 1000x that of a grape!  Similarly, think of the surface of the rinds of oranges vs apples vs bananas. They all serve the purpose of wrapping and protecting their fruit but their outer surface has different shapes and textures.

Introduction to layers

Epithelial linings can be in one layer or more than one layer:

1. Simple – one layer (as shown in Figure 1 – outlined in light blue)
   1. 1. Function: Generally lines blood vessels and body cavities to diffuse and regulate passage of materials between the two. Usually, the cell layer is very thin to help with diffusion.Fig 1. Slide of H&E stained lung alveoli with simple squamous type I pneumocytes marked out in blue and the cuboidal type II pneumocytes marked out in light green. (Slide ID: Path 304 030a, Image ID: 1556 – Lung)
2. Stratified – multiple layers (Figure 2 – outlined in light blue)
   1. 1. Function: protection against the environment, microbes and meant to shed off in layers.

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Keep in mind that the epithelial tissue (whether one layer thick or more) sits on top of the basement membrane with other tissues below.  So, at first glance, EVERYTHING looks stratified.  However, with practice, you will be able to identify the basement membrane which is the boundary between the basal surface of the epithelial tissue and a the deeper tissue (e.g. connective, muscle).  You will also notice that the pattern of cell shapes change as you go from epithelial tissue into deeper structures.

Introduction to alive vs dead cells

We don’t realize how many dead cells we carry upon our body.  As mentioned in the Metastatic Cancer: Melanoma chapter, our entire outer skin is actually dead cells.  So when looking at histological specimens, how can we tell if the tissue we are looking at is dead or alive?  Simply put, you look for the presence of a nucleus.  All living cells must have a functional nucleus to manage cellular functions, start the synthesis of products, and for cellular reproduction.  Thus, if you can see a nucleus that looks intact (i.e. not bits of degraded nucleus) – usually stained deeply purple with H&E – then that cell is alive.   Dead cells will still stain with H&E since there is still protein in the dead cell. But a stained nucleus will be absent.  This is obvious in Figure 2, where the yellow line denotes the layers of dead skin cells.

Figure 1 also has ‘dead cells’.  You can see red blood cells (RBCs) as the round red cells with the pale center. But RBCs lack nuclei and there is an absence of dark purple staining in RBCs. As outlined in the Blood, Anemia, Leukemia, and Blood Tests chapter, RBCs can not reproduce nor make any cellular product.  Thus, RBCs are not “alive” which is  disconcerting for some to hear as blood is considered the essence of human life!

Introduction of shapes

When looking at shapes of cells, we always look at the apical surface layer of epithelia. By its very nature, stratified cells can not have the same shape in every layer – purely because the layer on the apical surface  has a specific function whereas the function of the basal surface is to simply reproduce (thus creating the stratification).

1. Squamous = think SQUAshed like a fried egg! 

Figure 1  is a H&E stain of alveoli in lung tissue. The squamous cells are marked in blue while the cuboidal is marked in green. Squamous cells can also be distinguished based on their eye-like shape or like a fried egg.  The blue outlined cells are as if you are looking at a fried egg on its side. Additionally, if we were looking from the top instead of from the side in this cross section, the squamous layer would look like a whole bunch of fried eggs crowded in a pan:  so borders are irregular as is size of cells but the nucleus will be a dominant feature, with o pattern/logic to the placement of the yolks/nuclei.  The advantage of this is a lot of surface area for things like diffusion.

As mentioned earlier, the logic of the shape also helps up determine the general function of squamous epithelial linings. Because squamous is very flat but not very thick (like a fried egg), it is useful for easy diffusion of substances between two compartments.  Figure 1 is alveolar tissue in the lung where the squamous cells form a barrier between the air and the blood vessels.  The air is visible in the lumen space and the red blood cells are identifiable by the round red cells with NO stained nuclei.

Figure 2 is also squamous epithelial tissue  (outlined in light blue) but there are many layers, thus making it stratified squamous epithelial tissue.   Now, how and why do we know it’s stratified?  First off, there is a lot of layers (outlined in yellow) but there are no nuclei. Then you see a lot of layers (outlined in blue) which are stained similarly with a ‘basement’ layer that’s shaped in waves.  Because we can count many nuclei between that basement layer and the identifiable squamous layer of the apical surface, we know that this must be stratified.

So why stratified in skin?  Well, you may recall from the Metastatic Cancer: Melanoma chapter that we are actually protected by a layer of DEAD skin over our living stratified squamous epithelial tissue.  Thus, the layers outline in yellow are dead – and that’s why there is no identifiable purple nuclei. These dead layers are shed off as a form of protection over our living skin.

So with the two functions lined out, it’s easy to see that squamous cells must be thin to allow easy diffusion between body cavities and blood vessels which gives it its “squashed” thinness. It also must be long and flexible to accommodate its stratified form where it’ll go through wear and tear to protect the body.

2.  Cuboidal (cell shaped as rounded squares, containing “strings of purple beads/pearls”)

For cuboidal lining epithelia, the cells may have different shapes but the nucleus are generally very round and evenly space.  An analogy is that the nuclei in a layer of cuboidal looks like a string of pearls.

Figures 3 & 4 show simple and stratified cuboidal cells, respectively.  In Figure 3, the nuclei are generally very round (highlighted in green), even though the cells may have different shapes and not quite perfectly cuboid.  So why the large, round nucleus in a cuboid shape?  Let’s think about function and shape logic again:  cuboidal cells are generally found in glandular tissues (e.g. sweat gland) and kidney tubules to secrete substances into a duct for transport elsewhere. Since cuboidal needs to make product (e.g. proteins), it needs a large nucleus for synthesis.  Since cuboidal cells surround the opening of a duct for the purpose of secretion, it can be thought that its more voluminous cuboid shape gives room to create and secrete substances.

3.  Columnar (rounded rectangles with basally located, oval nuclei)

Columnar cells are recognized by their rectangular shapes and elongated, oval nucleus which sit near the bottom of the cell (side closest to the basement membrane) all lined up in a row

The literal shape of a columnar cell says a lot about its function. A large nucleus suggest a lot of nuclear activity (E.g. synthesis of proteins). A long cytoplasm separating the nucleus from the apical surface suggests a lot of cellular machinery needed to process the nuclear product.  Finally, the apical surface of the columnar cells sometimes have special features like cilia or microvilli (noted in green boxes).

There are two major functions for columnar cells:  secretion of product or absorption from the apical surface.  These well known functions of columnar cells explains why they can be found in the  epithelial lining the gastrointestinal tract, amongst other locations.

The epithelia of the GI tract makes a lot of substances to secrete (e.g. mucous). Thus columnar cells are ideal for its machinery.  The epithelia of the small intestine has the purpose of absorption of nutrients.  Previously, we had stated that squamous epithelia is ideal for absorption due to its surface area. However, columnar cells can actually provide greater surface area than squamous shape with the special apical feature of microvilli.  Microvilli increase surface area but needs the appropriate cytoskeleton for it to project out of the apical surface.  Thus microvilli are seen in columnar cells as it has ample room to ‘anchor’ the microvilli. In Figure 5, the microvilli are noted by green boxes in the simple columnar epithelia. As with simple squamous, note that there is a single layer of columnar with microvilli as absorption needs only 1 cell thickness. Compare that with Figure 6 where stratified columnar is necessary due to the harsh chemical environment that the stratified columnar epithelia line in the kidney tubules.

In summary, your body wants to be as efficient in absorption as possible to extract the most amount of nutrients and energy possible from foodstuffs. With thin columnar cells lining the GI tract, they are able to maximize absorption with their special feature – microvilli. Many columnar cells have special features like microvilli, cilia etc. because of its elongated shape which is “deep enough” to anchor these apical features.

4.  Transitional – bunched rounded layers, transitions between bunched cuboidal and stretched squamous 

As the name implies, transitional epithelia is epithelia that undergoes sudden transitions.  The most common location for transitional epithelia is the bladder epithelia which goes through rapid changes in volume throughout the day.  Transitional epithelia has to accommodate for these swings in volume by being ‘stretchy’, rather than relying on changing cell numbers.

In Figure 7, transitional epithelium is easy to identify with its signature umbrella or raindrop shape cells at the top of the layer. Since this type of epithelium lines most urinary tracts and bladder it needs to be able to stretch well which is what the “umbrella” shape allows for.

An analogy for transitional is a marshmallow.  When allowed its natural shape, a marshmallow is tall and columnar. But if you apply weight to the marshmallow, it can compress to a cuboidal or even a squamous shape. But once that weight is released, the marshmallow springs back to its columnar shape. Thus, a marshmallow can have different heights and volume dependent on the force applied to it, without changing its mass.

2. Pseudostratified

Pseudostratified columnar epithelia is only present in respiratory and reproductive systems and so is generally ciliated.  Cilia allows for movement – whether brushing mucous away from airways or ova away from the ovaries.   Pseudostratified columnar is a difficult layer type to recognize as it has virtually no visual difference from stratified columnar epithelium, at first glance (see Figure 8).

 But if given the chance to compare layer thickness with a true stratified epithelial lining, the difference in thickness is abundantly clear.  The nuclei in pseudostratified, noted by the green line in Figure 9,  are mismatched at different heights which differentiates it from the more neatly layered cuboidal and columnar stratified epithelia in Figures 4 & 6, respectively. Although the nuclei are mismatched, if one traces each nuclei to its respective basal surface, we recognize that each nucleated cell is in contact with the basement membrane, thus making it a simple layer which happens to ‘look’ stratified. Hence the name ‘pseudostratified’.  

So why make pseudostratified when stratified can do a better job?  It is possible that there is a need for differently sized columnar cells for protection. As one columnar cell is damaged, there is another columnar cell ready to takes its place, albeit shorter.  But an immediate shorter replacement is better than having to wait for the mitosis of a new columnar cell.